Collaborative membrane activity and receptor-dependent tumor cell targeting for precise nanoparticle delivery in CXCR4 colorectal cancer.

Clicks: 343
ID: 50911
2019
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Abstract
By the appropriate selection of functional peptides and proper accommodation sites, we have generated a set of multifunctional proteins that combine selectivity for CXCR4 cell binding and relevant endosomal escape capabilities linked to the viral peptide HA2. In particular, the construct T22-GFP-HA2-H6 forms nanoparticles that upon administration in mouse models of human, CXCR4 colorectal cancer, accumulates in primary tumor at levels significantly higher than the parental T22-GFP-H6 HA2-lacking version. The in vivo application of a CXCR4 antagonist has confirmed the prevalence of the CXCR4 tumor tissue selectivity over unspecific cell penetration, upon systemic administration of the material. Such specificity is combined with improved endosomal escape, what overall results in a precise and highly efficient tumor biodistribution. These data strongly support the functional recruitment as a convenient approach to generate protein materials for clinical applications. More precisely, they also support the unexpected concept that enhancing the unspecific membrane activity of a protein material does not necessarily compromise, but it can even improve, the selective cell targeting offered by an accompanying functional module. STATEMENT OF SIGNIFICANCE: We have shown here that the combination of cell-penetrating and tumor cell-targeting peptides dramatically enhances precise tumor accumulation of protein-only nanoparticles intended for selective drug delivery, in mouse models of human colorectal cancer. This fact is a step forward for the rational design of multifunctional protein nanomaterials for improved cancer therapies.
Reference Key
sala2019collaborativeacta Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Sala, Rita;Sánchez-García, Laura;Serna, Naroa;Céspedes, María Virtudes;Casanova, Isolda;Roldán, Mònica;Sánchez-Chardi, Alejandro;Unzueta, Ugutz;Vázquez, Esther;Mangues, Ramón;Villaverde, Antonio;
Journal Acta biomaterialia
Year 2019
DOI
S1742-7061(19)30614-2
URL
Keywords
colorectal cancer cxcr4 active targeting fusogenic peptide protein materials self-assembling

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